Subcortical surface morphometry in substance dependence: An ENIGMA addiction working group study.

While imaging studies have demonstrated volumetric differences in subcortical structures associated with dependence on various abused substances, findings to date have not been wholly consistent. Moreover, most studies have not compared brain morphology across those dependent on different substances of abuse to identify substance-specific and substance-general dependence effects. By pooling large multinational datasets from 33 imaging sites, this study examined subcortical surface morphology in 1628 nondependent controls and 2277 individuals with dependence on alcohol, nicotine, cocaine, methamphetamine, and/or cannabis. Subcortical structures were defined by FreeSurfer segmentation and converted to a mesh surface to extract two vertex-level metrics-the radial distance (RD) of the structure surface from a medial curve and the log of the Jacobian determinant (JD)-that, respectively, describe local thickness and surface area dilation/contraction. Mega-analyses were performed on measures of RD and JD to test for the main effect of substance dependence, controlling for age, sex, intracranial volume, and imaging site. Widespread differences between dependent users and nondependent controls were found across subcortical structures, driven primarily by users dependent on alcohol. Alcohol dependence was associated with localized lower RD and JD across most structures, with the strongest effects in the hippocampus, thalamus, putamen, and amygdala. Meanwhile, nicotine use was associated with greater RD and JD relative to nonsmokers in multiple regions, with the strongest effects in the bilateral hippocampus and right nucleus accumbens. By demonstrating subcortical morphological differences unique to alcohol and nicotine use, rather than dependence across all substances, results suggest substance-specific relationships with subcortical brain structures.

Mega-Analysis of Gray Matter Volume in Substance Dependence: General and Substance-Specific Regional Effects.

OBJECTIVE: Although lower brain volume has been routinely observed in individuals with substance dependence compared with nondependent control subjects, the brain regions exhibiting lower volume have not been consistent across studies. In addition, it is not clear whether a common set of regions are involved in substance dependence regardless of the substance used or whether some brain volume effects are substance specific. Resolution of these issues may contribute to the identification of clinically relevant imaging biomarkers. Using pooled data from 14 countries, the authors sought to identify general and substance-specific associations between dependence and regional brain volumes. METHOD: Brain structure was examined in a mega-analysis of previously published data pooled from 23 laboratories, including 3,240 individuals, 2,140 of whom had substance dependence on one of five substances: alcohol, nicotine, cocaine, methamphetamine, or cannabis. Subcortical volume and cortical thickness in regions defined by FreeSurfer were compared with nondependent control subjects when all sampled substance categories were combined, as well as separately, while controlling for age, sex, imaging site, and total intracranial volume. Because of extensive associations with alcohol dependence, a secondary contrast was also performed for dependence on all substances except alcohol. An optimized split-half strategy was used to assess the reliability of the findings. RESULTS: Lower volume or thickness was observed in many brain regions in individuals with substance dependence. The greatest effects were associated with alcohol use disorder. A set of affected regions related to dependence in general, regardless of the substance, included the insula and the medial orbitofrontal cortex. Furthermore, a support vector machine multivariate classification of regional brain volumes successfully classified individuals with substance dependence on alcohol or nicotine relative to nondependent control subjects. CONCLUSIONS: The results indicate that dependence on a range of different substances shares a common neural substrate and that differential patterns of regional volume could serve as useful biomarkers of dependence on alcohol and nicotine.

Acute alcohol effects on set-shifting and its moderation by baseline individual differences: a latent variable analysis.

AIMS: To compare the acute effects of alcohol on set-shifting task performance (relative to sober baseline performance) during ascending and descending limb breath alcohol concentration (BrAC), as well as possible moderation of these effects by baseline individual differences. DESIGN: Shifting performance was tested during an initial baseline and a subsequent drinking session, during which participants were assigned randomly to one of three beverage conditions (alcohol, placebo or control) and one of two BrAC limb conditions [ascending and descending (A/D) or descending-only (D-only)]. SETTING: A human experimental laboratory on the University of Missouri campus in Columbia, MO, USA. PARTICIPANTS: A total of 222 moderate-drinking adults (ages 21-30 years) recruited from Columbia, MO and tested between 2010 and 2013. MEASUREMENTS: The outcome measure was performance on set-shifting tasks under the different beverage and limb conditions. Shifting performance assessed at baseline was a key moderator. FINDINGS: Although performance improved across sessions, this improvement was reduced in the alcohol compared with no-alcohol groups (post-drink latent mean comparison across groups, all Ps ≤ 0.05), and this effect was more pronounced in individuals with lower pre-drink performance (comparison of pre- to post-drink path coefficients across groups, all Ps ≤ 0.05). In the alcohol group, performance was better on descending compared with ascending limb (P ≤ 0.001), but descending limb performance did not differ across the A/D and D-only groups. CONCLUSIONS: Practising tasks before drinking moderates the acute effects of alcohol on the ability to switch between tasks. Greater impairment in shifting ability on descending compared with ascending breath alcohol concentration is not related to task practice.

Automatic approach bias towards smoking cues is present in smokers but not in ex-smokers.

RATIONALE: Drug-addicted individuals show automatic approach tendencies towards drug-related cues, i.e., an approach bias (ApB). Nevertheless, little is known about ApB in tobacco smokers and about the presence of ApB after smoking abstinence. OBJECTIVES: We investigated ApB to smoking cues in heavy tobacco smokers versus never-smokers and studied its relation to smoking characteristics and craving. Second, we compared ApBs of heavy smokers with biases of abstinent heavy smokers. METHOD: A group of current heavy smokers (n = 24), ex-smokers who were abstinent for at least 5 years (n = 20), and never-smokers (n = 20) took part in the experiment. An indirect smoking approach avoidance task was performed, in which participants were required to respond to pictures of smoking and neutral cues by pulling (approach) or pushing (avoid) on a joystick, according to the content-irrelevant format of the picture (landscape or portrait). Craving scores were examined using the Questionnaire of Smoking Urges. RESULTS: Heavy smokers showed an ApB for smoking cues compared to ex-smokers and never-smokers, which correlated positively to craving scores. There were no group differences in ApB scores for ex-smokers and never-smokers. CONCLUSION: These results suggest that ApBs for smoking cues are present in heavy smokers and decrease after long-term successful smoking cessation.